Strong Collagen Hydrogels By Oxidized Polysaccharide Modification

Tissue engineering is the efficient way to tackle the life-threatening challenge of organ failure or tissue loss, one of the most difficult and thorny medical problems in the world. At present, the key point or the basis of the tissue engineering is to build an applicable three-dimensional matrices based on biomedical materials, which act as the analogues to the natural ECM. From the structural perspective, natural ECMs are gels composed of various protein fibrils and fibers interwoven within a fully hydrated network of glycosaminoglycan chains. Hydrogels are also highly hydrated networks and share the same structural character with the natural ECM. Therefore, hydrogels have been of great interest in the tissue engineering field as matrices for repairing and regenerating a wide variety of tissues and organs, which act as the temporary extracellular matrix (ECM) to direct the growth and formation of a desired tissue. Collagen plays a dominant role in maintaining the biologic and structural integrity of ECM. Due to its abundant and sustainable resource, cell adhesive peptides and good biocompatibility, non-antigenic, and controllable cell-based biodegradability, collagen hydrogel has been widely used as tissue engineering scaffold. However, the poor mechanical properties of collagen hydrogel are the main disadvantage to prevent it from the wide application.In this paper, we use aldehyde-functionalized dextran, which is prepared from the oxidation of another natural polymer dextran, as a macromolecular crosslinker to enhance the strength of the collagen hydrogel. The morphological and structural difference, between the pristine collagen hydrogel and the collagen/aldehyde-functional ized dextran (Col/DAD) hydrogels, is confirmed by SEM, AFM, FTIR, compression test and rheology analysis, etc. The mechanism of the hydrogel formation is studied preliminarily by the introduction of guanidine hydrochloride, which is capable of breaking hydrogen bonds and hydrophobic interaction. The resulted Col/DAD hydrogels are much stronger and present better thermostability than the pristine collagen hydrogel as expected. The maximum compression strength of the Col/DAD hydrogel is about 20 times larger than that of the pristine collagen hydrogel. After 24 h incubation at 37℃, the final G’ of Col/DAD hydrogel is more than 10 times than that of the pristine collagen hydrogel. Besides, there is also great improvement for the thermostability. We also prove that our method maintains the good biocompatibility of the collagen hydrogel and does not bring the cytotoxicity often seen from conventional chemical crosslinking in the product. Therefore, the strong collagen hydrogel made by oxidized dextran modification may have the great potential in tissue engineering and other biomedical fields.We also use aldehyde-functionalized cellulose, another polysaccharide derivative, which is prepared from the oxidation of another natural polymer cellulose, as a macromolecular crosslinker to enhance the strength of the collagen hydrogel. Compared with the pristine collagen hydrogel, the resulted collagen/aldehyde-functionalized cellulose (Col/DAC) hydrogels are much stronger and show better thermostability. The maximum compression strength of the Col/DAC hydrogel is more than 10 times than that of the pristine collagen hydrogel. Moreover, the Col/DAC hydrogel presents good biocompatibility. Based on our study, just like Col/DAD hydrogel in our previous study, the main components of the Col/DAC hydrogel present favorable biocompatibility and biodegradability, which makes it suitable for the wide application as cell and drug carrier in the biomedical material field.